The 5-phthalancarbonitrile compound of the formula [VI] ##STR2##
(hereinafter to be also referred to as compound [VI]) is a compound useful as a synthetic intermediate for citalopram of the formula [VII] ##STR3##
which is an antidepressant. The production method of the 5-phthalancarbonitrile compound is known to be as shown in the following scheme (WO98/19511). ##STR4##
wherein R is cyano, alkyloxycarbonyl having 2 to 6 carbon atoms or alkylaminocarbonyl having 2 to 6 carbon atoms, and Hal is a halogen atom.
According to this method, when R is other than cyano, cyanation is necessary after reduction and ring closure reaction. For example, when R is alkyloxycarbonyl, cyanation is carried out by the three steps of hydrolysis, amidation and reaction with chlorosulfonyl isocyanate, and when R is alkylaminocarbonyl, cyanation is carried out by a reaction with thionyl chloride or phosphorus pentachloride. In these methods, reagents undesirable to the environment, such as chlorosulfonyl isocyanate, thionyl chloride and phosphorus pentachloride, are used, and when R is alkyloxycarbonyl, cyanation is carried out by 3 steps, which is not necessarily simple or easy.
When R is cyano, the production method of the starting material, 5-cyanophthalide, needs to be improved. To be specific, 5-cyanophthalide is known to be obtained by the reaction of a diazonium salt derived from 5-aminophthalide with potassium cyanide in the presence of copper sulfide (Bull. Soc. Sci. Bretagne, 26, 1951, 35). This method is not desirable in that a toxin and a heavy metal salt are involved, such as potassium cyanide and copper sulfide. In addition, synthesis of 5-aminophthalide requires a dangerous reaction of nitration of phthalimide (Organic Synthesis II, 459), and further, reduction to amino by tin chloride and semi-reduction of phthalimide by zinc (J. Chem. Soc., 1931, 867), generating a waste heavy metal that is industrially undesirable.
It is therefore an object of the present invention to provide a production method of a 5-phthalancarbonitrile compound, which places only a small burden on the environmental and which is safe.